Influenza A reassortant viruses that contain human influenza hemagglutinin and neuraminidase genes and the six internal genes from the A/Mallard/78 (H2N2) avian influenza donor virus were readily generated in vitro and were attenuated for monkeys and man. An avian-human influenza reassortant containing only an M gene or NP gene from the avian virus was attenuated for monkeys. The internal six genes of two additional avian virus also effected restriction of viral replication in primates. The avian hemagglutinin and neuraminidase genes are required for enterotropism in ducks. The H2 hemagglutinin gene specifies restricted replication in nasal turbinates of hamsters. Synthetic peptides representing a wide range of regions on the H3(75) hemagglutinin stimulate antibodies that bind to the hemagglutinin; however, immunization of hamsters with these peptides did not induce resistance to challenge.